title: Progesterone receptor membrane component 1 as the mediator of the inhibitory effect of progestins on cytokine-induced matrix metalloproteinase 9 activity in vitro.
abstract: Progesterone (P4) and the progestin, 17α-hydroxyprogesterone caproate, are clinically used to prevent preterm births (PTBs); however, their mechanism of action remains unclear. Cytokine-induced matrix metalloproteinase 9 (MMP-9) activity plays a key role in preterm premature rupture of the membranes and PTB. We demonstrated that the primary chorion cells and the HTR8/SVneo cells (cytotrophoblast cell line) do not express the classical progesterone receptor (PGR) but instead a novel progesterone receptor, progesterone receptor membrane component 1 (PGRMC1), whose role remains unclear. Using HTR8/SVneo cells in culture, we further demonstrated that 6 hours pretreatment with medroxyprogesterone acetate (MPA) and dexamethasone (Dex) but not P4 or 17α-hydroxyprogesterone hexanoate significantly attenuated tumor necrosis factor α-induced MMP-9 activity after a 24-hour incubation period. The inhibitory effect of MPA, but not Dex, was attenuated when PGRMC1 expression was successfully reduced by PGRMC1 small interfering RNA. Our findings highlight a possible novel role of PGRMC1 in mediating the effects of MPA and in modulating cytokine-induced MMP-9 activity in cytotrophoblast cells in vitro.
authors.affiliation: 1Department of Anesthesiology, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Terrence K
authors.initials: TK
authors.lastname: Allen
authors.forename: Liping
authors.initials: L
authors.lastname: Feng
authors.forename: Chad A
authors.initials: CA
authors.lastname: Grotegut
authors.forename: Amy P
authors.initials: AP
authors.lastname: Murtha
mesh_terms: D002460:Cell Line; D002823:Chorion / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005321:Extraembryonic Membranes / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008565:Membrane Proteins / Q000502:physiology*; D011372:Progestins / Q000494:pharmacology*; D011980:Receptors, Progesterone / Q000502:physiology*
chemical_list: D016207:Cytokines; D008565:Membrane Proteins; C115296:PGRMC1 protein, human; D011372:Progestins; D011980:Receptors, Progesterone; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: inflammation; preterm delivery; progesterone; progesterone receptor